52P Modified FOLFIRINOX Versus CISGEM As First-Line Chemotherapy for Advanced Biliary Tract Cancer: Results of AMEBICA PRODIGE 38 Randomized Phase II Trial

Combination chemotherapy (CT) with cisplatin and gemcitabine (CISGEM) is the first-line standard of care for patients with advanced biliary tract cancers (BTC). FOLFIRINOX demonstrated an overall survival (OS) improvement in metastatic pancreatic adenocarcinoma compared to gemcitabine monotherapy. We aimed to compare FOLFIRINOX to CISGEM in advanced BTC. This open-label, randomized phase II-III study was carried out in 43 French centers. Patients with locally advanced (unresectable) or metastatic BTC, ECOG PS 0-1, were randomly assigned (1:1 ratio) to receive either modified FOLFIRINOX (mFOLFIRINOX, without 5FU bolus at day 1) or CISGEM for 6 months. The primary endpoint in phase II was the progression-free survival rate at 6 months (PFS6) according to RECIST v1.1. 94 patients per arm were needed to test the H1 hypothesis that PFS6 was ≥ 60% (one-sided alpha=5%, power=85%, 73% is expected). 190 patients were randomized (mFOLFIRINOX, 94; CISGEM, 96). Among them, 185 were evaluable (modified intention to treat population, mITT) for the primary endpoint (n=92 and 93, respectively). After a median follow-up of 21 months, the primary endpoint was not reached in the mFOLFIRINOX arm, with a PFS6 of 44.6% [90%CI: 35.7-53.7]. Median PFS (mITT) was 6.2 months [95%CI: 5.5-7.8] in the mFOLFIRINOX arm versus 7.4 months [95%CI: 5.6-8.7] in the CISGEM arm. Median OS was 11.7 months [95%CI: 9.5-14.2] versus 14.3 months [95%CI: 11.3-16.5] respectively. The disease control rates were 66.2% and 69.9% respectively (mainly stable disease). Rates of grade 3-4 adverse events were similar in the mFOLFIRINOX (72.8%) and CISGEM (72.0%) arms, mainly digestive (28.3% vs. 12.9%) and hematologic (32.6% vs. 57.0%). First-line chemotherapy with mFOLFIRINOX did not meet the primary endpoint. CISGEM remains the first-line standard of care for advanced BTC.